Molecular dynamics (MD) simulations of VIP and PACAP27

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide-27 (PACAP27) are members of the secretin-glucagon family containing 28 and 27 residues, respectively. NMR spectroscopy studies suggest that the N-terminus exhibit consecutive beta-turns whereas the central and C-terminal parts of the VIP molecule have been characterized as being two alpha-helices. In contrast, similar studies carried out on PACAP suggest that the shortest active peptide segment PACAP27 in the presence of trifluoroethanol (TFE) exhibits a disordered N-terminal domain followed by a alpha-helix expanding residues 9-26 with a discontinuity between residues 20 and 21. In the present study, a series of MD trajectories of VIP and PACAP27 were carried out using two different implicit models of the solvent: the Generalized Born that use an effective Born radii described by Onufriev, Bashford, and Case (GBOBC) and the Hawkins, Cramer, and Truhlar approximation (GBHCT) and two different force fields: AMBER ff99 and a modified version of the latter described by Sorin and Pande (Biophys J 2005, 88, 2472-2493), ff99SP. Comparison of the structures obtained from the MD trajectories and those derived from the NMR studies in the literature indicates that the GBOBC method is more efficient in the exploration of the conformational space and presents a higher agreement with the experimental structure of VIP and PACAP27 in TFE.